PhD Thesis Project (M/F) Cell identity and lineage plasticity in the lung metastatic niche

Institut Curie Siège
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Date de clôture
Lieu(x) de travail
Orsay
Secteur
Centre de Recherche
CDD
Institut Curie is a major player in the research and fight against cancer. It consists of a Hospital group and a Research Center of more than 1000 employees with a strong international representativeness.
The objective of the Research Center is to develop basic research and to use the knowledge produced to improve the diagnosis, prognosis, and therapeutics of cancers as part of the continuum between basic research and innovation serving the patient.

Laboratory

The team “RNA, Tumor Microenvironment and Metastasis”, led by Albertas Navickas, has been recently established at Institut Curie, in the “Genome Integrity, RNA and Cancer” (UMR3348) department in Orsay. We focus on the gene regulatory networks promoting the establishment of the metastatic niche. For this, we combine single cell genomics with the tissue modelling ex vivo using human stem cell-derived organoids. More information is accessible at https://institut-curie.org/team/navickas.

 

Our team is affiliated to the Doctoral School 582 “Oncology: Biology, Medicine, Health” at Paris-Saclay University. The full application procedure can be found at https://www.universite-paris-saclay.fr/en/doctoral-schools/doctoral-school-oncology-biology-medicine-health#edit-group-home.

 

Description of the PhD thesis project

Metastasis is the main reason behind cancer−related mortality, with limited therapeutic opportunities currently available. Due to complicated detection and modeling in mice, numerous events early in the metastatic cascade remain yet to be elucidated. Here, we leverage the human stem cell−derived lung organoid differentiation to model the lung metastatic niche conditioning by breast cancer cells ex vivo. Our preliminary data show that we can recapitulate multiple molecular events associated with breast cancer progression, induced by a co-culture of human lung organoids and breast cancer cells. We detected that metastatic breast cancer cells but not normal mammary epithelium induced cell fate changes in the lung organoid compartment. This project proposes to systematically dissect cell fate trajectories in the lung metastatic niche by applying the lineage tracing technology in the ex vivo model, and then identify the underlying gene regulatory mechanisms. We will apply functional genetics tools to validate our findings ex vivo, and use breast cancer patient data to further assess the clinical relevance of our results. We anticipate to link the early cellular plasticity events in the lung metastatic niche with breast cancer progression.

Keywords. Breast cancer; metastasis; hPSC; lung organoids; metastatic niche; cellular fate; lineage tracing; gene regulation.

The complete description of the project can be found on the ADUM platform: www.adum.fr

 

Candidate Profile

  • Training and Skills required
    • Training: Master’s degree in Biology or equivalent.
    • Scientific skills: Understanding the principles of gene regulation in the context of molecular, cell and developmental biology.
    • Professional experience desirable: general lab experience. Experience in the techniques of molecular, cell or developmental biology is a plus.
    • Language skills: fluent French and English

 

  • Abilities
    • Ability to work independently, managerial abilities, aptitude for working in a team
    • Ability to communicate

 

 

All our opportunities are open to people with disabilities

Contract information

  • Type of contract: Fixed-term contract, doctoral school fellowship from Paris-Saclay University
  • Starting date: October 1, 2022
  • Duration: 3 years
  • Working time: full time
  • Remuneration: according to the current grids
  • Benefits: Collective catering, reimbursement of transportation fees up to 70%, supplementary health insurance
  • Location of the position: Orsay
  • Reference: 2022-03-3348DOCNAV

 

Contact

Please send your CV, letter of motivation to Albertas Navickas (albertas.navickas@curie.fr).

 

Publication date: 18/03/20022

Deadline for application: 30/04/2022

Exemple : +33112365489
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